(94a) Continuous Biochemical Reactor Design Utilizing Optimization Under Optimal Control Constraints

Continuous operation can be used in bioprocesses to allow for increased cell viability through the mitigation of substrate and product inhibition, thereby increasing the productivity of the desired product. However, the dilution rate, feed glucose composition, reactor geometry and effluent piping geometry must first be determined, as they play a key role as parameters affecting the maximum productivity in a continuous bioreactor system. This work looks to simultaneously examine the reactor design and control problem through the use of an optimal control problem as a constraint to the optimal reactor design problem. In this way we can simultaneously determine the optimal reactor design and dynamic operation conditions capable of achieving the maximum production of a desired product when produced via continuous operation. A carotene production process will be utilized as a case study for the described algorithm. First, a two-level parameter estimation method is utilized to develop a reliable kinetic model for the batch production of carotenoids via fermentation to describe the glucose consumption, metabolic product formation and depletion, and the carotenoid production in the Saccharomyces cerevisiae strain mutant SM14 with glucose as the carbon source. These models are then extended to the design of a novel continuous bioreactor that uses a two feed configuration that gives the ability to use flowrate and glucose concentration of the feed stream as independent manipulated variables. A bi-level optimization algorithm is implemented to determine the optimal design of the continuous bioreactor for which the optimal control problem governing the dilution rate and glucose concentration is satisfied. From this algorithm the optimal bioreactor geometry is determined as well as the optimal profiles of the manipulated variables necessary to achieve the maximum possible production rate of the carotene product.